Lyme disease is a tick-borne infection with worldwide distribution caused by Borrelia burgdorferi sensu lato. Borrelia burgdorferi sensu stricto (hereinafter referred to as "B. burgdorferi") initially causes a flu-like systemic illness that, if untreated, may develop into a disease characterized by arthritic, cardiac and neurological involvement {Steere, A. C., N. Eng. J. Med., 321:586-596 (1989)}. Although the clinical manifestations of Lyme disease have been well documented, basic knowledge relating the pathogenesis of Lyme borreliosis to specific molecular components, specifically outer membrane (OM) proteins, has been lacking due primarily to the lability of the OM of B. burgdorferi {Luft, B. J., Infect. & Immun., 57:3637-3645 (1989)}. Since OM proteins presumably mediate the host/pathogen interaction, identification and characterization of these molecules may provide important insights into the molecular pathogenesis of Lyme disease.
There are two distinct features of the outer membrane of pathogenic spirochetes which have hindered the characterization of their constituent outer membrane proteins. The outer membrane of pathogenic spirochetes are extremely labile, resulting in the loss of a significant amount of the outer membrane, even under the mildest experimental conditions. In addition, this labile outer membrane of B. burgdorferi has been shown by freeze fracture electron microscopy to contain at least 5-fold less transmembrane outer membrane proteins than that of typical enteric gram negative bacteria {Walker, E. M., et al., J. Bacteriol., 173:5585-5588 (1991)}. This fragility of the outer membrane and paucity of outer membrane proteins has made the application of standard outer membrane purification techniques to spirochetes unsuccessful.
The majority of molecular studies pertaining to Lyme disease have focused on lipoproteins designated Osp which are localized to both the inner and outer membrane of B. burgdorferi {Brusca, J. S., et al., J. Bacteriol., 173:8004-8008 (1991); Norris, S. J. et al., Infect. Immun., 60:4662-4672 (1992)}. Proteins that span the OM of B. burgdorferi, or OM-spanning ("Oms") proteins have only been visualized by freeze-fracture electron microscopy {Walker, E. M., et al., J. Bacteriol., 173:5585-5588 (1991); Radolf, J. D., et al J. Bacteriol., 176:21-31 (1994)} and have not been molecularly characterized.